The Impact of Photobiomodulation Therapy on Enhancing Spermatogenesis and Blood-Testis Barrier Integrity in Adult Male Mice Subjected to Scrotal Hyperthermia.

Introduction: Unhealthy lifestyle choices such as alcohol, chemicals, and heat stress can worsen male infertility. Heat stress can cause damage to the essential structure known as the blood-testis barrier (BTB). Photobiomodulation therapy (PBMT) has been employed in various studies to enhance sperm quality in individuals with genital inflammatory conditions in recent times. The current research sought to study how laser therapy affects spermatogenesis and the structure of the BTB in a mouse model of scrotal heat exposure. Methods: Thirty adult male NMRI mice, 8 weeks old, were divided into three groups: Control, Hyperthermia, and Hyperthermia+Laser 0.03 J/cm2. The animals in the hyperthermia group had their testicles exposed to water at 43 °C for 20 minutes five times every other day. Then, the testicles were exposed to laser radiation every other day for 35 days, lasting 3 minutes each time, with an energy density of 0.03 J/cm2. Animals were sacrificed, and sperm parameters, reactive oxygen species (ROS) and glutathione (GSH) levels, stereological parameters, and gene expression were assessed in the end. Results: The study showed that PBMT can significantly enhance sperm quality, quantity of spermatogenic cells, testicular volume, levels of ROS and GSH, and gene expression related to the blood-testis barrier. Conclusion: Currently, PBMT is a novel approach for addressing male infertility by preserving the integrity of the BTB in Sertoli cells, which in turn supports the growth and specialization of germ cells.

Therapeutic effects of curcumin nanoemulsion on cyclophosphamide-induced testicular toxicity in adult male mice.

Objective: Several chemotherapeutic agents, including cyclophosphamide (CP) and busulfan, have been shown to interfere with spermatogenesis. Accordingly, the main objective of this study was to evaluate the potential therapeutic effects of curcumin nanoemulsion (CUR-NE) on spermatogenesis in mice with CP-induced testicular toxicity. Methods: A total of 28 adult male mice were equally divided into four groups: control, CUR-NE (30 mg/kg, daily for 5 weeks), CP (200 mg/kg, single dose), and CP+CUR-NE. Each group was evaluated regarding sperm parameters, DNA fragmentation index, chromatin maturation, reactive oxygen species (ROS) levels, and histological parameters of the testes. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone, and testosterone were also assessed in all groups. Results: In CP-induced mice, CUR-NE treatment significantly improved sperm parameters, including total sperm count, motility, morphology, and DNA integrity. CUR-NE administration was also associated with significantly higher serum levels of testosterone and FSH, as well as testis weight and volume, in the mice treated with CP. Furthermore, CUR-NE treatment significantly increased the number of spermatogonia, primary spermatocytes, round spermatids, and Leydig cells in the testicular tissue of these animals. A marked reduction in ROS levels in the testes tissue was observed following administration of CUR-NE to CP-induced mice. Conclusion: CUR-NE appears to promote spermatogenesis in mice with CP-induced testicular toxicity by reducing ROS levels, improving testicular stereological parameters, and strengthening the reproductive hormone profile.

Maternal exposure to phenanthrene induces testicular apoptosis and Sertoli cell dysfunction in F1 adult male mice: a histological and molecular study.

Objective: Phenanthrene, a polycyclic aromatic hydrocarbon, is found in abundance in environmental pollutants, food, and drinking water. This substance can accumulate in body tissues and exert harmful effects. Moreover, phenanthrene can cross the placental barrier, potentially impacting fetal development. We aimed to explore the impacts of maternal exposure to phenanthrene on testicular tissue and Sertoli cell function in F1 mice. Methods: Female rats with vaginal plugs were randomly assigned to one of three groups: control, sham, or phenanthrene. The control group received no intervention during pregnancy. In the sham and phenanthrene groups, corn oil and a phenanthrene solution, respectively, were administered via gavage once every 2 days. Offspring were separated by sex 21 days after birth. At 56 days postnatal, male F1 offspring were euthanized, and their testes were harvested for histological and molecular analyses. Results: Phenanthrene exposure was associated with a lower testicular weight and volume, a smaller diameter of the seminiferous tubules, and a relative thinning of the germinal epithelium. These changes were associated with increased cellular apoptosis, as shown by the upregulation of caspase 3 expression. Additionally, we observed an increase in vacuolization and residual bodies within the tissue. Conversely, the number of Sertoli cells and expression levels of Sox9, as well as the Ocln and Itgb1 genes, were found to be lowered. Conclusion: Maternal exposure to phenanthrene impacts both germ cells and Sertoli cells, disrupting their function and leading to fertility disorders in male F1 offspring mice.

The effects of vitamin C and vitamin B12 on improving spermatogenesis in mice subjected to long-term scrotal heat stress.

Objective: Scrotal hyperthermia poses a significant threat to spermatogenesis and fertility in mammalian species. This study investigated the effects of vitamin B12 and vitamin C on spermatogenesis in adult male mice subjected to long-term scrotal hyperthermia. The rationale is based on the sensitivity of germ cells and epididymal sperm to increased scrotal temperatures. While various factors, both internal and external, can raise the testicular temperature, this study focused on the potential therapeutic roles of vitamins B12 and C. Methods: After inducing scrotal hyperthermia in mice, vitamin B12 and vitamin C were administered for 35 days. We assessed sperm parameters, serum testosterone levels, stereological parameters, the percentage of apoptotic cells, reactive oxygen species (ROS) levels, and glutathione (GSH) levels. Additionally, real-time polymerase chain reaction was used to analyze the expression of the c-kit, stimulated by retinoic acid gene 8 (Stra8), and proliferating cell nuclear antigen (Pcna) genes. Results: Vitamin C was more effective than vitamin B12 in improving sperm parameters and enhancing stereological parameters. The study showed a significant decrease in apoptotic cells and a beneficial modulation of ROS and GSH levels following vitamin administration. Moreover, both vitamins positively affected the expression levels of the c-kit, Stra8, and Pcna genes. Conclusion: This research deepens our understanding of the combined impact of vitamins B12 and C in mitigating the effects of scrotal hyperthermia, providing insights into potential therapeutic strategies for heat stress-related infertility. The findings highlight the importance of considering vitamin supplementation as a practical approach to counter the detrimental effects of elevated scrotal temperatures on male reproductive health.

Therapeutic Effects of Exosome Therapy and Photobiomodulation Therapy on the Spermatogenesis Arrest in Male Mice After Scrotum Hyperthermia.

Introduction: In men, several factors cause infertility, among which we can mention damage to sperm due to high temperature. So far, various treatments have been proposed for it, but they have not been highly effective. The current study aimed to evaluate the effect of exosome therapy (EXO) and photobiomodulation therapy (PBMT) on spermatogenesis arrest in male mice after scrotum hyperthermia. Methods: In this experimental study, the animals were divided into four groups: control, scrotal hyperthermia, scrotal hyperthermia+EXO (100 µL/d) (mice were treated for 30 days), scrotal hyperthermia+PBMT (laser of 0.03 J/cm2 for 30 seconds/for 30 days). Hyperthermia was induced by exposure to the temperature of 43 °C for 20 minute every day for 5 times. After 6 weeks, the animals were sacrificed. Results: The treated groups showed a significant increase in sperm parameters, as compared to the hyperthermic groups. Moreover, these favorable effects were observed in relation to the volume of testicular tissue, the number of germ cells, Leydig cells and Sertoli cells, and the level of testosterone. Research on antioxidants showed a significant reduction in oxidized glutathione (GSSG) and reactive oxygen species (ROS) in the treatment groups in comparison to the hyperthermia group (P<0.001). Also, there has been a significant increase in the amount of hydrogen peroxide enzyme observed in the hyperthermia group as opposed to the treatment group (P<0.001). Conclusion: These findings show that EXO and PBMT can improve spermatogenesis caused by hyperthermia, reduce ROS and GSSG, and increase glutathione (GSH) and sperm quality.

Sertoli cell-conditioned medium can improve blood-testis-barrier function and spermatogenesis in azoospermia mice induced by scrotal hyperthermia: An experimental study.

Background: An increase in the temperature of the testis is associated with damage to the epithelium of seminiferous tubules and disruption of sperm production. Objective: The current study aimed to investigate the effect of the Sertoli cell-conditioned medium (SCCM) on the blood-testis-barrier associated genes and spermatogenesis process following scrotal hyperthermia. Materials and Methods: In this experimental study, 40 adult NMRI mice (8 wk, 25-30 gr) were allocated into 4 groups: I) control, II) DMEM (10 µl Dulbecco's Modified Eagle Medium), III) scrotal hyperthermia, and IV) scrotal hyperthermia+SCCM (10 µl SCCM). Hyperthermia was induced by placing the mice scrotum in water at 43 C for 20 min every other day for 10 days. Mice were treated every other day for 5 wk. Then the animals were euthanized, and the tails of epididymis were removed to analyze sperm parameters, testis were taken for stereological assessment, reactive oxygen spices and glutathione levels, and the expression of Ocln, Gja1, Cdh2, and Itgb1. Results: The results of sperm analysis indicated that SCCM-treated mice significantly increased sperm count and motility and reduced DNA fragmentation. In addition, histological and molecular findings showed that the volume of testicular tissue, the number of germ cells, the glutathione level, and the expression of Ocln, Gja1, Cdh2, and Itgb1 genes were significantly increased in the SCCM-treated mice. Conclusion: Findings suggest that growth factors of SCCM stimulate the proliferation and differentiation of germ cells through paracrine effects and upregulate the blood-testis-barrier-associated genes in mice subjected to scrotal hyperthermia.

Exploring Intercellular Dynamics: Ultra-Weak Biophoton Emission as a Novel Indicator of Altered Cell Functions and Disease in Oligospermia Mice.

Introduction: Biophoton emission, the spontaneous release of photons from living cells, has emerged as an attractive field of research in the study of biological systems. Scientists have recently discovered that changes in biophoton emission could serve as potential indicators of pathological conditions. This intriguing phenomenon suggests that cells might communicate and interact with each other through the exchange of these faint but significant light signals. Therefore, the present study introduces intercellular relationships with biophoton release to detect normal and abnormal cell functions to further achieve cellular interactions by focusing on cell and cell arrangement in disease conditions. Methods: Twenty male mice were assigned to control and busulfan groups. Five weeks after the injection of busulfan, the testis was removed, and then the stereological techniques and TUNEL assay were applied to estimate the histopathology of the testis tissue sections. Results: The findings revealed that the ultra-weak biophoton emission in the control group was significantly lower than in the busulfan group. The oligospermia mice model showed that it significantly changed the spatial arrangement of testicular cells and notably decreased the testis volume, length of seminiferous tubules, and the number of testicular cells. The results of the TUNEL assay showed that the percentage of apoptotic cells significantly increased in the busulfan group. Conclusion: The ultra-weak biophoton emission from testis tissue was reduced in oligospermia mice. As a result, the decline of ultra-weak biophoton can indicate a change in cell arrangement, a decrease in intercellular interaction, and eventually disease.

An elderberry-supplemented diet improves spermatogenesis in mice with busulfan-induced azoospermia.

CONTEXT: Approximately 40-50% of all infertility cases are due to male infertility, and one of the most important causes of infertility is azoospermia. AIMS: This study aimed to evaluate the potential effect of elderberry on the spermatogenesis process in the azoospermia mice model. METHOD: Thirty adult male mice were randomised into three groups: control; busulfan (45mg/kg); and busulfan+elderberry (2%), 6mL orally per animal. Sperm samples were collected from the tail of the epididymis, and testis specimens were also collected and then subjected to sperm parameters analysis, histopathological evaluation, reactive oxygen species (ROS), and glutathione (GSH) measurement to determine the mRNA expression and hormonal assay. CONCLUSIONS: It can be concluded that the elderberry diet may be considered a complementary treatment to improve the spermatogenesis process in busulfan-induced azoospermic mice. IMPLICATIONS: Considering some limitations, the elderberry diet can be an alternate option for improving testicular damage following chemotherapy.

Therapeutic Effects of Edaravone on Azoospermia: Free Radical Scavenging and Autophagy Modulation in Testicular Tissue of Mice.

Background: Chemotherapeutic agents such as cyclophosphamide and busulfan have been shown to have a negative impact on the spermatogenesis process. Based on this fact, the objective of this study was to investigate the effects of edaravone on spermatogenesis in busulfan-induced mice. Methods: Forty adult male mice were equally divided into the four groups: 1) control, 2) edaravone, 3) busulfan, and 4) busulfan + edaravone. Then, the sperm parameters, histopathological examinations, and serum levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also assessed. Caspase-3, Beclin-1, and ATG-7 mRNA levels were also determined using real-time PCR. Results: Our results revealed that treatment of mice with edaravone in busulfan-induced azoospermia significantly improves sperm parameters, including total count, morphology, and viability (p<0.05). Furthermore, edaravone administration led to a significant increase in serum testosterone (p<0.0001) and FSH (p<0.001) levels, as well as testis weight (p<0.05) and volume (p<0.01). Edaravone also prevented a decrease in the number of testicular cells including spermatogonia (p<0.0001), primary spermatocytes (p<0.001), round spermatids (p<0.0001), Sertoli (p<0.01), and Leydig cells (p<0.0001) in busulfan-treated mice. Additionally, in busulfan-induced azoospermia, edaravone significantly reduced the percentage of sperm with immature chromatin (p<0.0001). Following treatment with edaravone, a decrease in reactive oxygen species (ROS) and an increase in glutathione (GSH) production were noted compared to busulfan-treated mice. Furthermore, caspase-3 (p<0.05), Beclin-1, and ATG-7 (p<0.001) genes expression decreased significantly in treatment groups compared to busulfan-induced azoospermia. Conclusion: According to our findings, edaravone can improve spermatogenesis in busulfan-induced azoospermia through free radical scavenging and autophagy modulation in testicular tissue.

Potential anti-inflammatory effect of Lamium album extract through caspase-3 and cyclooxygenase-2 genes expression in a rat model of middle cerebral artery occlusion.

INTRODUCTION: Stroke is one of the most common causes of death worldwide. Inflammation and apoptosis play an important role in the cascade of ischemic stroke.

Combined molecular, structural and memory data unravel the destructive effect of tramadol on hippocampus.

Tramadol is a synthetic analogue of codeine and stimulates neurodegeneration in several parts of the brain that leads to various behavioral impairments. Despite the leading role of hippocampus in learning and memory as well as decreased function of them under influence of tramadol, there are few studies analyzing the effect of tramadol administration on gene expression profiling and structural consequences in hippocampus region. Thus, we sought to determine the effect of tramadol on both PC12 cell line and hippocampal tissue, from gene expression changes to structural alterations. In this respect, we investigated genome-wide mRNA expression using high throughput RNA-seq technology and confirmatory quantitative real-time PCR, accompanied by stereological analysis of hippocampus and behavioral assessment following tramadol exposure. At the cellular level, PC12 cells were exposed to 600 µM tramadol for 48 hrs, followed by the assessments of ROS amount and gene expression levels of neurotoxicity associated with neurodegenerative pathways such as apoptosis and autophagy. Moreover, the structural and functional alteration of the hippocampus under chronic exposure to tramadol was also evaluated. In this regard, rats were treated with tramadol at doses of 50 mg/kg for three consecutive weeks. In vitro data revealed that tramadol provoked ROS production and caused the increase in the expression of autophagic and apoptotic genes in PC12 cells. Furthermore, in-vivo results demonstrated that tramadol not only did induce hippocampal atrophy, but it also triggered microgliosis and microglial activation, causing upregulation of apoptotic and inflammatory markers as well as over-activation of neurodegeneration. Tramadol also interrupted spatial learning and memory function along with long-term potentiation (LTP). Taken all together, our data disclosed the neurotoxic effects of tramadol on both in vitro and in-vivo. Moreover, we proposed a potential correlation between disrupted biochemical cascades and memory deficit under tramadol administration.

Implantation of human olfactory ecto-mesenchymal stem cells restores locomotion in a rat model of Parkinson's disease.

One of the complex neurodegenerative disorders is Parkinson disease (PD). PD is mainly caused by dopaminergic (DAergic) neuron degeneration in the midbrain. The loss of DAergic neurons is considered as a key reason of motor functional defects in PD patients. Cell replacement strategies are considered as an alternative remedy to effectively address neurodegeneration in PD. In this report, we evaluated the restorative effect of human olfactory ecto-mesenchymal stem cells (OE-MSCs) in rat models of PD. Accordingly, human OE-MSCs were isolated and phenotypically characterized by flow cytometry and immunocytochemistry. Next, the undifferentiated OE-MSCs were unilaterally transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rat models, followed by molecular and histological analyzes as well as assessment of motor skills. Our results displayed that the grafting of OE-MSCs increased the expression of DAergic markers namely dopamine transporter (DAT), tyrosine hydroxylase (TH), nuclear receptor related-1 (Nurr1) in a 6-OHDA model compared with that of control, detected by immunohistochemical staining and western blot. Moreover, noticeable improvements in motor coordination, muscle activity and locomotor performance were observed in 6-OHDA model of PD following OE-MSCs transplantation. Taken together, our finding indicates that undifferentiated OE-MSCs might be counted as an appropriate source for cell replacement therapy particularly aimed at PD.

Chronic Exposure to Tramadol Induces Neurodegeneration in the Cerebellum of Adult Male Rats.

Tramadol is a centrally acting synthetic opioid analgesic and SNRI (serotonin/norepinephrine reuptake-inhibitor) that structurally resembles codeine and morphine. Given the tramadol neurotoxic effect and the body of studies on the effect of tramadol on the cerebellum, this study aims to provide deeper insights into molecular and histological alterations in the cerebellar cortex related to tramadol administration. In this study, twenty-four adult male albino rats were randomly and equally divided into two groups: control and tramadol groups. The tramadol group received 50 mg/kg of tramadol daily for 3 weeks via oral gavage. The functional and structural change of the cerebellum under chronic exposure of tramadol were measured. Our data revealed that treating rats with tramadol not only lead to cerebellum atrophy but also resulted in the actuation of microgliosis, neuroinflammatoin, and apoptotic biomarkers. Our results illustrated a significant drop in VEGF (vascular endothelial growth factor) level in the tramadol group. Additionally, tramadol impaired motor coordination and neuromuscular activity. We also identified several signaling cascades chiefly related to neurodegenerative disease and energy metabolism that considerably deregulated in the cerebellum of tramadol-treated rats. Overall, the outcomes of this study suggest that tramadol administration has a neurodegeneration effect on the cerebellar cortex via several pathways consisting of microgliosis, apoptosis, necroptosis, and neuroinflammatoin.

Curcumin-Loaded Iron Particle Improvement of Spermatogenesis in Azoospermic Mouse Induced by Long-Term Scrotal Hyperthermia.

Spermatogenesis process is sensitive to heat stress because the testicular temperature is 2 to 4 °C lower than the core body temperature. The current study aimed to investigate the effects of iron oxide nanoparticles containing curcumin on spermatogenesis in mice induced by long-term scrotal hyperthermia. In this experimental study, 18 mice were equally divided into the following three groups: control, scrotal hyperthermia, and scrotal hyperthermia + curcumin-loaded iron particles (NPs) (240 µL) (mice were treated for 20 days). Hyperthermia was induced by exposure to the temperature of 43 °C for 20 min every other day for 5 weeks. Afterward, the animals were euthanized; sperm samples were collected for sperm parameters analysis, and testis samples were taken for histopathology experiments, evaluation of serum testosterone level, and RNA extraction in order to examine the expression of c-kit, STRA8 and PCNA genes. Our study showed that curcumin-loaded iron particles could notably increase the volume of testis, length of seminiferous tubules, sperm parameters, and stereological parameters (i.e., spermatogonia, primary spermatocyte, round spermatid, and Leydig cells) thereby increasing serum testosterone level; in addition, TUNEL-positive cells showed a significant decrease in curcumin-loaded iron particle group. Thus, based on the obtained results, the expression of c-kit, STRA8, and PCNA genes was significantly increased in treatment groups by curcumin-loaded iron particles compared with scrotal hyperthermia-induced mice. In conclusion, curcumin-loaded iron particles can be considered an alternative treatment for improving the spermatogenesis process in scrotal hyperthermia-induced mice.

Bilateral striatal transplantation of human olfactory stem cells ameliorates motor function, prevents necroptosis-induced cell death and improves striatal volume in the rat model of Huntington's disease.

Cellular transplant therapy is one of the most common therapeutic strategies used to mitigate symptoms of neurodegenerative diseases such as Huntington's disease (HD). Briefly, the main goal of the present study was to investigate HD's motor deficits through the olfactory ecto-mesenchymals stem cells (OE-MSC) secretome. OE-MSCs were characterized immunophenotypically by the positive expression of CD73, CD90 and CD105. Also, three specific markers of OE-MSCs were obtained from the nasal cavity of human volunteers. The main features of OE-MSCs are their high proliferation, ease of harvesting and growth factor secretion. All animals were randomly assigned to three groups: control, 3-NP + vehicle treated and 3-NP + Cell groups. In both experimental groups, the subjects received intraperitoneal 3-NP (30 mg/kg) injections once a day for five consecutive days, followed by the bilateral intra-striatal implantation of OE-MSCs in the 3-NP + Cell group. Muscular function was assessed by electromyography and rotarod test, and the locomotor function was evaluated using the open field test. According to our findings, striatal transplants of OE-MSCs reduced microglial inflammatory factor, the tumor necrosis factor (TNFα) in the 3-NP + Cell group, with a significant reduction in RIP3, the markers of necroptosis in striatum. In addition to the remarkable recovery of the striatal volume after engraftment, the motor activities were enhanced in the 3-NP + cell group compared to the 3-NP + vehicle group. Taken together, our results demonstrated the in vivo advantages of OE-MSCs treatment in an HD rat model with numerous positive paracrine effects including behavioral and anatomical recovery.

Chronic administration of methylphenidate did not affect memory and GDNF levels but increase astrogliosis in adult male rat's hippocampus.

BACKGROUND: ADHD is the most common developmental disorder affecting approximately three to seven percent of school-aged children and 2.5 percent of adults worldwide. The drug of choice for the pharmacotherapy of ADHD is Methylphenidate (MPH). However, there is growing concerns about side effects resulting from its potential interference with brain anatomical and behavioral development. AIM: This article focuses on the adverse effects of MPH on the rat's hippocampus. METHODS: The animals received an oral dose of 5 mg/kg MPH or normal saline, as the vehicle, on a daily basis for 30 days. Y-maze test, passive avoidance, Barnes maze and field potential recording were conducted. Western blot for detecting the neurotrophic factor of GDNF and immunohistochemistry of astrogliosis were performed. RESULTS: Our results revealed that MPH treatment suppressed the willingness of rats to explore new environments. Also, it had no effect on improving long-term potentiation, long-term memory and spatial memory in the MPH group as opposed to the control group. There was also a significant increase of astrogliosis in the treated rats' hippocampi. On the other hand, there was not a significant relationship between MPH administration and the decrement of the GDNF level. CONCLUSION: We encourage the need to conduct more research on the adverse effects of MPH on the brain.

Tramadol exposure upregulated apoptosis, inflammation and autophagy in PC12 cells and rat's striatum: An in vitro- in vivo approach.

AIM AND BACKGROUND: Tramadol is a synthetic analogue of codeine, mostly prescribed for the alleviation of mild to moderate pains. It bears several side effects including emotional instability and anxiety. In this study, we focused on the alteration in expression of autophagic and apoptotic genes in PC-12 cells for our in vitro and structural and functional changes of striatum for our in vivo under chronic exposure of tramadol. METHODS: For in vitro side of the study, PC12 cells were exposed to tramadol (50 µM) and expression of apoptosis and autophagy genes were determined. In parallel, rats were daily treated with tramadol at doses of 50 mg/kg for three weeks for the in vivo side. Motor coordination, EMG, histopathology and gene expression were done. RESULTS: Our in vitro findings revealed that tramadol increased expression of apoptosis and autophagy genes in PC12 cells. Moreover, our in vivo results disclosed that tramadol not only provoked atrophy of rats' striatum, but also triggered microgliosis along with neuronal death in the striatum. Tramadol also reduced motor coordination and muscular activity. CONCLUSION: Altogether, our data indicated that tramadol induced neurotoxicity in the PC12 cells via apoptosis and autophagy and in striatum chiefly through activation of neuroinflammatory and apoptotic responses.

Tramadol: a Potential Neurotoxic Agent Affecting Prefrontal Cortices in Adult Male Rats and PC-12 Cell Line.

Tramadol is a synthetic analogue of codeine that is often prescribed for the treatment of mild to moderate pains. It has a number of side effects including emotional instability and anxiety. In this study, we focus on the structural and functional changes of prefrontal cortex under chronic exposure to tramadol. At the cellular level, the amounts of ROS and annexin V in PC12 cells were evidently increased upon exposure to tramadol (at a concentration of 600 µM for 48 h). To this end, the rats were daily treated with tramadol at doses of 50 mg/kg for 3 weeks. Our findings reveal that tramadol provokes atrophy and apoptosis by the induction of apoptotic markers such as Caspase 3 and 8, pro-inflammatory markers, and downregulation of GDNF. Moreover, it triggers microgliosis and astrogliosis along with neuronal death in the prefrontal cortex. Behavioral disturbance and cognitive impairment are other side effects of tramadol. Overall, our results indicate tramadol-induced neurodegeneration in the prefrontal cortex mainly through activation of neuroinflammatory response.

Photobiomodulation restores spermatogenesis in the transient scrotal hyperthermia-induced mice.

OBJECTIVE: Heat stress shock affects the generation of free radicals and can have a harmful effect on spermatogenesis. Photobiomodulation (PBM) is very effective in andrology for treating male infertility. This research aimed at the evaluation of the impacts of PBM on spermatogenesis on the transient scrotal hyperthermia-induced oligospermia mouse model. MATERIALS AND METHODS: This experimental research divided 24 mice into the following four groups: (1) Control, (2) Scrotal hyperthermia, (3) Scrotal hyperthermia receiving laser 0.03 J/cm2 for 30 s for each testis, 35 days after induction of scrotal hyperthermia every other day for 35 days, and (4) Scrotal hyperthermia receiving laser 0.03 J/cm2 for 30 s for each testis, immediately after induction of scrotal hyperthermia every other day for 35 days. Scrotal hyperthermia was induced by water bath with 43 °C for 30 min. Then, the mice were euthanized, and their sperm samples were collected for sperm parameters analysis. Then, we took the testis samples for histopathological experimentations, serum testosterone level, reactive oxygen species (ROS), RNA extraction for the examination of IL1-α, IL6 and TNF-α genes expression as well as production and glutathione disulfide (GSH) activity. KEY FINDINGS: Our outputs indicated that PBM could largely improve the sperms parameters and stereological parameters, like spermatogonia, primary spermatocyte, round spermatid and Leydig cells together with an increasing level of the serum testosterone and GSH activity compared to the scrotal hyperthermia induced mice. In addition, it was found that the diameter of seminiferous tubules, ROS production, as well as the expression of IL1-α, IL6, and TNF-α genes significantly decreased in the treatment groups by PBM compared to the scrotal hyperthermia induced mice, but there was not a significant difference in terms of testis weight and Sertoli cells between the studied groups. SIGNIFICANCE: It could be concluded that PBM may be regarded as an alternative treatment for improving the spermatogenesis process in the scrotal hyperthermia induced mice.

Effect of Sertoli Cell Transplantation on Reducing Neuroinflammation-Induced Necroptosis and Improving Motor Coordination in the Rat Model of Cerebellar Ataxia Induced by 3-Acetylpyridine.

To date, no certain cure has been found for patients with degenerative cerebellar disease. In this trial, we examined the in vivo and in vitro neuroprotective effects of Sertoli cells (SCs) on alleviating the symptoms of cerebellar ataxia. Testicular cells from an immature male rat were isolated and characterized by immunocytochemical analysis for somatic cell markers (anti-Mullerian hormone, vimentin). The protein assessment had already confirmed the expression of neurotrophic factors of glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial factor (VEGF). In vitro neuroprotective impact of SCs was determined after exposing PC12 cells to Sertoli cell-conditioned media (SC-CM) and H2O2, simultaneously. Afterwards, ataxia rat models were induced by a single dose of 3-AP (3-acetylpyridin), and 3 days later, SCs were bilaterally implanted. Motor and neuromuscular activity test were conducted following SC transplantation. Finally, immunohistochemistry against RIPK3 and Iba-1 was done in our generation. The in vivo results revealed substantial improvement in neuromuscular response, while ataxia group exhibited aggravated condition over a 28-day period. Our results suggested enhanced motor function and behavioral characteristics due to the ability of SCs to suppress necroptosis and consequently extend cell survival. Nevertheless, more studies are required to affirm the therapeutic impacts of SC transplantation in human cerebellar ataxia. In vitro data indicated cell viability was increased as a result of SC-CM with a significant reduction in ROS.